Effects of oral bisphosphonate therapy on serum calcium in elderly veterans with poor kidney function

Limited data exist on the use of bisphosphonates in patients with poor kidney function due to a contraindication derived from inadequate experience among patients with kidney failure, accounting for as much as 25% of nonprescribing when otherwise appropriate.

To determine whether bisphosphonate use in patients with decreased renal function, as outlined in the package insert (estimated creatinine clearance [eCrCl] <35 mL/min), would result in higher rates of hypocalcemia, as suggested in previous studies.

This was a retrospective cohort study of elderly veterans 65 years of age and older at the Veterans Affairs North Texas Health Care System in Dallas, Texas. We identified 3089 patients who started oral bisphosphonate therapy between August 1, 2003 and July 12, 2010. Of the 252 patients meeting the inclusion criteria, 25 and 227 patients had an eCrCl <35 mL/min and eCrCl ≥35 mL/min, respectively. Analyses of changes in serum calcium from baseline to the 1-year study end point were performed within and between each renal function group.

Among the veterans with an eCrCl <35 mL/min and eCrCl ≥35 mL/min, there were decreases in median serum calcium levels from baseline to study end point from 9.8 mg/dL (interquartile range [IQR], 9.4-10.2 mg/dL) to 9.3 mg/dL (IQR, 9.0-10.0 mg/dL; P = 0.028) and 9.6 mg/dL (IQR, 9.3-9.9 mg/dL) to 9.4 mg/dL (IQR, 9.1-9.8 mg/dL; P < 0.001), respectively. However, there was no difference in Δcalcium: -0.2 mg/dL (IQR, 0-0.6 mg/dL) and 0.2 mg/dL (IQR, -0.2 to 0.5 mg/dL; P = 0.547), respectively.

This exploratory assessment may suggest that, in elderly veterans, the initiation of oral bisphosphonate therapy contributed to a statistically significant decrease in serum calcium levels regardless of baseline renal function; however, the clinical impact of this change does not appear to be significant. Future studies should assess serum calcium in a larger population of patients to confirm the safety of oral bisphosphonates in poor kidney function.